Water → [2-{4-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidinyl}ethyl] 4-methoxybenzoate

HRID 1856575Notes

Reaction equation

HRID 1856575 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]=[C:10]2[NH:18][CH:19]2[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][OH:27])[CH2:21][CH2:20]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:35][O:36][C:37]1[CH:45]=[CH:44][C:40]([C:41](Cl)=[O:42])=[CH:39][CH:38]=1.O>ClCCl>[CH3:35][O:36][C:37]1[CH:45]=[CH:44][C:40]([C:41]([O:27][CH2:26][CH2:25][N:22]2[CH2:23][CH2:24][CH:19]([NH:18][C:10]3[N:9]([CH2:8][C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)[C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=4[N:11]=3)[CH2:20][CH2:21]2)=[O:42])=[CH:39][CH:38]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7477p-Anisoyl chlorideHCID 8471TriethylamineHCID 128916994-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidineethanol

Product 1

HCID 12891731[2-{4-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidinyl}ethyl] 4-methoxybenzoateYield 43.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred mixture of 4.5 parts of 4-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidineethanol, 2 parts of N,N-diethylethanamine and 195 parts of dichloromethane is added dropwise a solution of 1.7 parts of 4-methoxybenzoyl chloride in dichloromethane. Upon completion, stirring is continued overnight at room temperature. Water is added and the layers are separated. The organic phase is dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (98:2 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The residue is converted into the hydrochloride salt in 2-propanone. The salt is filtered off and dried, yielding 2.5 parts (43.5%) of [2-{4-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidinyl}ethyl] 4-methoxybenzoate; dihydrochloride. hemihydrate; mp. 189.2° C.

Workup

  1. customthe layers are separated
  2. customThe organic phase is dried
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue is purified by column-chromatography over silica gel using
  6. additiona mixture of trichloromethane and methanol (98:2 by volume) as eluent
  7. customThe pure fractions are collected
  8. customthe eluent is evaporated
  9. filtrationThe salt is filtered off
  10. customdried

Sources & evidence

ORD record
ord-87c785952cc14b0ba7f7c82cfc22e0c0
Source dataset
uspto-grants-1980_08
Patent number
US04219559

Reaction notes

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